Ovarian transcriptomic analysis reveals differential expression genes associated with prenatal mortality for litter size in rabbits
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ABSTRACT: Transcriptomic profiles could help understand the prenatal mortality after selection for ovulation rate. This study aims to perform the gene expression pattern in ovarian tissue using microarrays from females belonging to the selected line and control line. Our results showed genes which could explain a high ovulation rate associated with lower prenatal survival in selected line females.
Project description:BackgroundEnvironmental variance (VE) is partly under genetic control and has recently been proposed as a measure of resilience. Unravelling the genetic background of the VE of complex traits could help to improve resilience of livestock and stabilize their production across farming systems. The objective of this study was to identify genes and functional mutations associated with variation in VE of litter size (LS) in rabbits. To achieve this, we combined the results of a genome-wide association study (GWAS) and a whole-genome sequencing (WGS) analysis using data from two divergently selected rabbit lines for high and low VE of LS. These lines differ in terms of biomarkers of immune response and mortality. Moreover, rabbits with a lower VE of LS were found to be more resilient to infections than animals with a higher VE of LS.ResultsBy using two GWAS approaches (single-marker regression and Bayesian multiple-marker regression), we identified four genomic regions associated with VE of LS, on chromosomes 3, 7, 10, and 14. We detected 38 genes in the associated genomic regions and, using WGS, we identified 129 variants in the splicing, UTR, and coding (missense and frameshift effects) regions of 16 of these 38 genes. These genes were related to the immune system, the development of sensory structures, and stress responses. All of these variants (except one) segregated in one of the rabbit lines and were absent (n = 91) or fixed in the other one (n = 37). The fixed variants were in the HDAC9, ITGB8, MIS18A, ENSOCUG00000021276 and URB1 genes. We also identified a 1-bp deletion in the 3'UTR region of the HUNK gene that was fixed in the low VE line and absent in the high VE line.ConclusionsThis is the first study that combines GWAS and WGS analyses to study the genetic basis of VE. The new candidate genes and functional mutations identified in this study suggest that the VE of LS is under the control of functions related to the immune system, stress response, and the nervous system. These findings could also explain differences in resilience between rabbits with homogeneous and heterogeneous VE of litter size.
Project description:Breeding schemes for meat production in rabbits involved a three-way cross of specialized lines in which a paternal line inseminates maternal crossbred females. Paternal line or terminal sire are selected for growth traits, being the males used for the production of fertile dose at the insemination centres and farms. So high growth rate males must produce, in addition, semen in sufficient quantity and quality to meet the demand of insemination and, nevertheless, several studies have been showed that selection for growth have effects on reproduction performance in female and males. In rabbits, negative effects has been observed in ovulation induction, prenatal survival and genetic correlation to fertility. Many factors influence the production and quality of rabbit semen, management as collection frequency, environment (season or photoperiod, nutrition and genetic. Most of the previous studies have been focused in the effects of selection on the seminal and sperm parameters but, little attention has been paid to the protein seminal plasma or sperm composition and if these changes could be affect the fertility of seminal doses obtained from the paternal males. The aim of this study was to evaluate if selection program by daily gain in fattening period has changed seminal traits, plasma and sperm proteoma and, the fertility of semen when it is used in artificial insemination. To do this we uses two re-derived groups of paternal males obtained from vitrified embryos with a difference of 18 generations between both groups.
Project description:Breeding schemes for meat production in rabbits involved a three-way cross of specialized lines in which a paternal line inseminates maternal crossbred females. Paternal line or terminal sire are selected for growth traits, being the males used for the production of fertile dose at the insemination centres and farms. So high growth rate males must produce, in addition, semen in sufficient quantity and quality to meet the demand of insemination and, nevertheless, several studies have been showed that selection for growth have effects on reproduction performance in female and males. In rabbits, negative effects has been observed in ovulation induction, prenatal survival and genetic correlation to fertility. Many factors influence the production and quality of rabbit semen, management as collection frequency, environment (season or photoperiod, nutrition and genetic. Most of the previous studies have been focused in the effects of selection on the seminal and sperm parameters but, little attention has been paid to the protein seminal plasma or sperm composition and if these changes could be affect the fertility of seminal doses obtained from the paternal males. The aim of this study was to evaluate if selection program by daily gain in fattening period has changed seminal traits, plasma and sperm proteoma and, the fertility of semen when it is used in artificial insemination. To do this we uses two re-derived groups of paternal males obtained from vitrified embryos with a difference of 18 generations between both groups.
Project description:Breeding schemes for meat production in rabbits involved a three-way cross of specialized lines in which a paternal line inseminates maternal crossbred females. Paternal line or terminal sire are selected for growth traits, being the males used for the production of fertile dose at the insemination centres and farms. So high growth rate males must produce, in addition, semen in sufficient quantity and quality to meet the demand of insemination and, nevertheless, several studies have been showed that selection for growth have effects on reproduction performance in female and males. In rabbits, negative effects has been observed in ovulation induction, prenatal survival and genetic correlation to fertility. Many factors influence the production and quality of rabbit semen, management as collection frequency, environment (season or photoperiod, nutrition and genetic. Most of the previous studies have been focused in the effects of selection on the seminal and sperm parameters but, little attention has been paid to the protein seminal plasma or sperm composition and if these changes could be affect the fertility of seminal doses obtained from the paternal males. The aim of this study was to evaluate if selection program by daily gain in fattening period has changed seminal traits, plasma and sperm proteoma and, the fertility of semen when it is used in artificial insemination. To do this we uses two re-derived groups of paternal males obtained from vitrified embryos with a difference of 18 generations between both groups.
Project description:Breeding schemes for meat production in rabbits involved a three-way cross of specialized lines in which a paternal line inseminates maternal crossbred females. Paternal line or terminal sire are selected for growth traits, being the males used for the production of fertile dose at the insemination centres and farms. So high growth rate males must produce, in addition, semen in sufficient quantity and quality to meet the demand of insemination and, nevertheless, several studies have been showed that selection for growth have effects on reproduction performance in female and males. In rabbits, negative effects has been observed in ovulation induction, prenatal survival and genetic correlation to fertility. Many factors influence the production and quality of rabbit semen, management as collection frequency, environment (season or photoperiod, nutrition and genetic. Most of the previous studies have been focused in the effects of selection on the seminal and sperm parameters but, little attention has been paid to the protein seminal plasma or sperm composition and if these changes could be affect the fertility of seminal doses obtained from the paternal males. The aim of this study was to evaluate if selection program by daily gain in fattening period has changed seminal traits, plasma and sperm proteoma and, the fertility of semen when it is used in artificial insemination. To do this we uses two re-derived groups of paternal males obtained from vitrified embryos with a difference of 18 generations between both groups.
Project description:BackgroundEnvironmental variance (VE) is partially under genetic control, which means that the VE of individuals that share the same environment can differ because they have different genotypes. Previously, a divergent selection experiment for VE of litter size (LS) during 13 generations in rabbit yielded a successful response and revealed differences in resilience between the divergent lines. The aim of the current study was to identify signatures of selection in these divergent lines to better understand the molecular mechanisms and pathways that control VE of LS and animal resilience. Three methods (FST, ROH and varLD) were used to identify signatures of selection in a set of 473 genotypes from these rabbit lines (377) and a base population (96). A whole-genome sequencing (WGS) analysis was performed on 54 animals to detect genes with functional mutations.ResultsBy combining signatures of selection and WGS data, we detected 373 genes with functional mutations in their transcription units, among which 111 had functions related to the immune system, stress response, reproduction and embryo development, and/or carbohydrate and lipid metabolism. The genes TTC23L, FBXL20, GHDC, ENSOCUG00000031631, SLC18A1, CD300LG, MC2R, and ENSOCUG00000006264 were particularly relevant, since each one carried a functional mutation that was fixed in one of the rabbit lines and absent in the other line. In the 3'UTR region of the MC2R and ENSOCUG00000006264 genes, we detected a novel insertion/deletion (INDEL) variant.ConclusionsOur findings provide further evidence in favour of VE as a measure of animal resilience. Signatures of selection were identified for VE of LS in genes that have a functional mutation in their transcription units and are mostly implicated in the immune response and stress response pathways. However, the real implications of these genes for VE and animal resilience will need to be assessed through functional analyses.
Project description:Prenatal exposure to synthetic corticosteroids can significantly alter postnatal development through changes in neurotransmitters, peptides and their receptors, and thus having long-lasting behavioral effects. Some of these changes have been observed in animal experiments, others also in humans prenatally exposed to synthetic corticosteroids. Here, we focused on transcriptomic changes within the ARC of rats prenatally exposed to either betamethasone or saline. The expression of transcriptome has been assessed by novel computational tools to determine complex changes that may have life-long effects on phenotype, i.e., behavior. Total of 18,094 unigenes were quantified in the hypothalamic ARC of P14 male and female rats prenatally exposed to betametasone used in this experiment. Out of these genes, Kyoto Encyclopedia for Genes and Genomes (http://www.genome.jp) selected 112 for the dopaminergic synapse, 75 for the GABAergic and 97 for the glutamatergic synapse. We further analyzed composition, topology and modulatory networks of the genomic fabric of the dopaminergic, GABAergic, and glutamatergic synapse (the transcriptome of the most interconnected and stably expressed gene network responsible for specific transmission). Finally we investigated the M-bM-^@M-^\transcriptomic landscapeM-bM-^@M-^] of the GSF in the ARC of P14 males (M) and females (F) prenatally (G15) exposed to betamethasone (B) or saline (S). We combined in one measure (PWR = Pair-Wise Relevance) expression levels, controls and coordination of all pairs that can be formed by synapse genes with the other synapse genes, higher PWRs indicating larger influence of that gene pair to the fabric modulation. We found that prenatal exposure to betamethasone caused sex-dependent changes in the dopaminergic/GABA/glutamatergic synapse genes:. In males, 10 dopaminergic (9%), 4 GABAergic (5%) and 5 glutamatergic synapse genes (5%) were down-regulated. While in females, 9 dopaminergic (8%), 3 GABAergic (4%) and 6 glutamatergic (6%) synapse genes were downregulated. The data indicate that in both sexes the dopaminergic synapse was the most affected. In contrast, in control animals, no significant differences between male and female were present in these synapse genes. Since the most noticeable transcritpomic changes were found in the transcriptome of DA glutamatergic synapse, we investigated the expression of tyrosine-hydroxylase (TH) NMDA receptor subunits in the ARC. The western blot analyses and immunohistochemistry confirmed the sex-specific differences between prenatally betamethasone-exposed and saline-exposed P15 rats. Accordingly to the changes in gene expression, prenatal exposure to synthetic corticosteroids was associated with postnatal changes in behavior and susceptibility to certain types of seizures. While we did not find any significant impairements in normal behavioral patterns (open field activity), there was a sex-specific change in the novel object recognition test. We found that behavioral lateralization in females is lost after prenatal betamethasone exposure and both male and female prenatally betamethasone exposed rats were avoiding novelty. This trait is similar to children with autism and suggests that certain elements of autistic behaviors can be present after prenatal exposure to synthetic corticosteroids. Additionally, there were changes in the search patterns in the Morris water maze as well as in the Barnes maze. In conclusion, our work is consistent with findings of profound reprogramming changes in the brain after prenatal corticosteroid exposure associated with alterations cognitive functions and seizure susceptibility. Two-sexes (M, F) x two-condition (B = betamethasone prenataly exposed vs S = saline prenataly exposed) experiment. Biological replicates: 4 MS, 4 FS, 4 MB, 4 FB.
Project description:Prenatal adversity or stress can have long-term consequences on developmental trajec-tories and health outcomes. Although the biological mechanisms underlying these effects are poorly understood, epigenetic modifications, such as DNA methylation, have the potential to link early-life environments to alterations in physiological systems, with long-term functional impli-cations. We investigated the consequences of two prenatal insults, prenatal alcohol exposure (PAE) and food-related stress, on DNA methylation profiles of the rat brain during early devel-opment. As these insults can have sex-specific effects on biological outcomes, we analyzed epige-nome-wide DNA methylation patterns in prefrontal cortex, a key brain region involved in cogni-tion, executive function, and behavior, of both males and females. We found sex-dependent and sex-concordant influences of these insults on epigenetic patterns. These alterations occurred in genes and pathways related to brain development and immune function, suggesting that PAE and food-related stress may reprogram neurobiological/physiological systems partly through central epigenetic changes, and may do so in a sex-dependent manner. Such epigenetic changes may re-flect the sex-specific effects of prenatal insults on long-term functional and health outcomes and may have important implications for understanding possible mechanisms underlying fetal alco-hol spectrum disorder and other neurodevelopmental disorders.
Project description:Background: Prenatal alcohol exposure (PAE) is associated with alterations in numerous physiological systems, including the stress and immune systems. We have previously shown that PAE increases the course and severity of arthritis in an adjuvant-induced arthritis (AA) model. While the molecular mechanisms underlying these effects are not fully known, changes in neural gene expression are emerging as important factors in the etiology of PAE effects. As the prefrontal cortex (PFC) and hippocampus (HPC) play key roles in neuroimmune function, PAE-induced alterations to their transcriptome may underlie abnormal steady-state functions and responses to immune challenge. The current study examined brains from adult PAE and control females from our recent AA study to determine whether PAE causes long-term alterations in gene expression and whether these mediate the altered severity and course of arthritis in PAE females Methods: Adult females from PAE, pair-fed [PF], and ad libitum-fed control [C]) groups were injected with either saline or complete FreundM-bM-^@M-^Ys adjuvant. Animals were terminated at the peak of inflammation or during resolution (days 16 and 39 post-injection, respectively); cohorts of saline-injected PAE, PF and C females were terminated in parallel. Gene expression was analyzed in the PFC and HPC using whole genome mRNA expression microarrays. Results: Significant changes in gene expression in both the PFC and HPC were found in PAE compared to controls in response to ethanol exposure alone (saline-injected females), including genes involved in neurodevelopment, apoptosis, and energy metabolism. Moreover, in response to inflammation (adjuvant-injected females), PAE animals showed unique expression patterns, while failing to exhibit the activation of genes and regulators involved in the immune response observed in control and pair-fed animals. Conclusions: These results support the hypothesis that PAE affects neuroimmune function at the level of gene expression, demonstrating long-term effects of PAE on the CNS response under steady-state conditions and following an inflammatory insult. Key words: prenatal alcohol exposure (PAE), ethanol, inflammation, arthritis, gene expression, rat. 192 samples, including 20 hybridization replicates